tbuckley/cabot-search huggingface dataset:
Abstract 10990: The Prognostic Significance of Right Ventricular Dilation Assessed by Cardiac Magnetic Resonance Imaging in Heart Failure With Reduced Ejection Fraction
Authors: Abdallah Malkawi, Ahmed Altibi, Munthir Mansour, Juerg Schwitter, Andrea Guaricci, Pier-Giorgio Masci, Carlo De Cecco, Nazario Carrabba, Akos Varga-Szemes, Ambra Masi, Andrea Baggiano, Andrea Barison, chiara lanzillo, Chiara Martini, claudia moro, Daniele Andreini, Edoardo Conte, Mark Rabbat, Marta Focardi, Martina Perazzolo Marra, Massimo Lombardi, Monica Dobrovie, Nicola Gaibazzi, PATRIZIA PEDROTTI, Joseph Schoepf, Saima Mushtaq, Stefano Censi, Emily Tat, Jan Bogaert, Jordi Lozano Torres, Nicola Sverzellati, Guglielmo Marco, Annalaura Gismondi, Matteo Gravina, Cristina Presicci, Manuel De Lazzari, Alessandro Palumbo, Adele Valentini, Gabriella Di Giovine, Laura Fusini, Davide Margonato, Mauro Timpani, Alberto Nese, Mauro Pepi, Gloria Cicala, Giuseppe Muscogiuri, Valentina Lorenzoni, Gianluca Pontone, Subhi J Al'Aref
Journal: Circulation (2022)

Background: Quantitative volumetric assessment of the right ventricle (RV) can significantly enhance risk stratification in heart failure (HF), especially with the increasing availability of cardiac MRI (CMR). The prognostic value of RV dilation measured by RV end diastolic volume indexed to body surface area (RVEDVi) is not yet well established. In this analysis, we investigate the prognostic significance of RVEDVi measured by CMR in a stable HF cohort. Methods: We conducted a retrospective analysis on the DERIVATE registry, a large cohort of stable HF patients who underwent baseline CMR and echocardiography assessment. We used the cut-off value 90ml/m 2 as the upper limit of normal for CMR-derived RVEDVi. The primary outcome was all-cause mortality (ACM), while the secondary outcome was a composite of ACM and/or heart failure hospitalization (HFH). A Cox proportional hazard model was used to evaluate the association with outcomes. Results: 2,447 patients with HF and reduced ejection fraction (HFrEF) were included, with a median follow-up time of 959 days (IQR: 560-1590). Mean LVEF was 34.0 ± 10.8, mean age was 59.8 ± 14.0 years and 42% were females. Mean RVEDVi was 75.0 ± 29.4 ml/m 2 and 23.2% had an RVEDVi &gt;90 ml/m 2 . Elevated RVEDVi (&gt;90 ml/m 2 ) was significantly associated with an increased risk for ACM (aHR= 1.40, 95% CI [1.17-1.67] p =0.01) and the composite of ACM/HFH (aHR= 1.40, 95% CI [1.03-1.90] p = 0.03). Conclusion: In a large cohort of HFrEF undergoing baseline CMR, elevated RVEDVi was associated with an increased risk of ACM and ACM and/or HFH, independent of LV systolic function.
Abstract 10571: Causes of Early Mortality After Catheter Ablation of Ventricular Tachycardia in Patients With Reduced Left Ventricular Ejection Fraction
Authors: Min Choon Tan, Justin Z Lee, Abhishek Deshmukh, Komandoor Srivathsan, Win K Shen, Hicham El Masry, Luis Scott, Samuel Asirvatham, Yong-Mei Cha, Christopher J McLeod, Siva K Mulpuru
Journal: Circulation (2022)

Background: Recognition of the causes of early mortality after ventricular tachycardia (VT) ablation in patients with reduced left ventricular ejection fraction is an essential step toward improving post-procedural outcomes. Objective: This study sought to determine the causes of early mortality (≤30-days) after VT ablation in patients with reduced left ventricular ejection fraction and to understand further the circumstances surrounding death after the procedure. Methods: We performed a retrospective analysis of all patients undergoing VT ablation in patients with reduced left ventricular ejection fraction from January 1, 2013, to November 10, 2021, at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a detailed chart review of the electronic health record within the Mayo Clinic system and outside records. Results: A total of 503 patients (mean age 63 ± 13 years, 11.2% female) with EF &lt;50% were included in the study. The 30-day all-cause mortality rate was 5% (n=25), and the mortality rate due to a procedural complication was 0.4%. Among all 30-day deaths, recurrent VT was the most common primary cause of death (44%). This was followed by decompensated heart failure (28%), procedure-related death (8%), cerebrovascular accident (CVA) (4%), and infection (4%). Most patients (91%) who died from VT had the VT recurrence within three days of the ablation. 76% of patients with early mortality had delayed referral for VT ablation, and 72% opted for comfort care before death. Conclusions: The overall early mortality (≤30-days) rate after catheter ablation of VT in patients with reduced left ventricular ejection fraction was 5%, but the death rate directly due to a procedural complication was only 0.4%. The most common cause of death was recurrent VT, followed by heart failure. Further research into ablation strategies is vital to improving the safety, efficacy, and durability of VT ablation.
Abstract 10847: Tolerability of Sars-cov-2 Mrna Vaccines and Infection for Patients With History of Kawasaki Disease
Authors: Mikayla A Beckley, Aaron K Olson, Michael A Portman
Journal: Circulation (2022)

Introduction: Kawasaki disease (KD) and multisystem inflammatory syndrome in children from COVID-19 infections share overlapping symptoms, suggesting KD patients may be at risk for adverse outcomes from exposure to SARS-CoV-2 mRNA vaccine or infection. Through retrospective review of clinical outcome data, we determined tolerance of KD patients to SARS-CoV-2 antigen exposure. Methods: We evaluated two cohorts using an existing KD database of 826 patients and reviewed individual electronic medical records for the period spanning January 2020 through Jan 2022 via Epic Care Everywhere which includes Washington State immunization records. Vaccine cohort inclusion criteria were (1) age &amp;lt 21 years at immunization and (2) received one or more Pfizer-BioNTech or Moderna vaccine doses. The COVID-19 infection cohort included (1) age &amp;lt 21 years and (2) positive SARS-CoV-2 PCR or nuclear capsid IgG. Results: The vaccine cohort contained 153 patients with vaccine distribution by age subgroups shown in Figure 1. Pfizer-BioNTech vaccine was provided for 93.5% and the remaining received Moderna or a combination. 84.3% were fully vaccinated or received a third-dose booster. No clinically severe adverse events occurred including no vaccine-related hospitalizations or outpatient visits. The COVID-19 infection cohort included thirty-seven patients. No patients required hospitalization. The most common symptoms included low grade fever, fatigue, cough, and myalgia with resolution within a few days. Two patients, 9 and 19 years, had extended cough and fatigue for 3-4 weeks. One patient developed COVID-19 within 6 weeks of receiving IVIG for KD. Conclusions: COVID-19 infections and vaccinations are well tolerated in patients with preceding KD. No severe complications occurred in either cohort with only two patients exhibiting prolonged mild symptoms from COVID-19. This study provides assurance regarding vaccine safety and COVID-19 severity for parents of children with KD.
Abstract 10315: The Effect of Protease-Activated Receptor-1 Inhibition With Vorapaxar in Post-mi and Nstemi Patients on Selected Biomarkers Reflecting Endothelial Function
Authors: Dennis W Nilsen, Michelle Røysland, Thor Ueland, Pal Aukrust, Annika E Michelsen, Harry Staines, Ståle Barvik, Frederic Kontny, Jan Erik Nordrehaug, Vernon V Bonarjee
Journal: Circulation (2022)

Introduction: Biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has essentially focused on platelets. Follow-up (FU) time has been short, whereas in the current study, focus has been on endothelial function during both short- and long-term PAR-1 inhibition. Aim: To assess short- and long-term effects of vorapaxar (V) as compared to Placebo (PL) on the following biomarkers: Angiopoietin-2 (ANGPT2), Angiopoietin-like 4 (ANGPTL4), VEGF, ICAM-1, VCAM-1, E-Selectin (ESEL), von Willebrand Factor (VWF), Thrombomodulin (TM), PAI-1 and PAI-2. Methods: In an independent collective subproject performed in Norway, post-MI patients at steady state were recruited from the “Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients with Atherosclerosis” (TRA2ᵒP-TIMI 50) and NSTEMI patients were recruited from the “Thrombin Receptor Antagonist for Clinical Event Reduction in acute coronary syndrome” (TRACER) trial. Biomarkers were measured in duplicate by enzyme immunoassays (EIA) in citrated plasma at one month follow-up and at study completion (median 2.3 years) for subjects recruited from both trials. Results: Biomarkers were measured in 265 consecutive patients [age median 62.0 years (Q1-Q3: 55.0-68.0 years), males 83%] with at least one change from baseline value. Among these, biomarkers were available at both short- and long-term follow-up in 221 subjects. ANGPT2 increased significantly in V as compared to PL at 1-month follow-up in the total population (p=0.034), and in males in both post-MI (p=0.031) and NSTEMI subjects (p=0.012), respectively. ANGPTL4 increased (p=0.028) and PAI-2 decreased (p=0.025) significantly in the total population in favor of V at final FU. In the total post-MI subgroup and among males of that group, a short-term significant increase in ESEL in favor of V was observed, p=0.029 and p=0.018, respectively. Also, a transient significant increase in VWF (p=0.032) in favor of V was seen at one month in NSTEMI patients. Conclusions: Significant changes suggesting potential harmful effects in some biomarkers were observed during 1-month and long-term PAR-1 inhibition as compared to placebo in post-MI and acute coronary syndrome patients.
Abstract 10475: Serial Inflammatory Cytokine Levels Are Increased in Atrial Fibrillation After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy
Authors: Dae H Lee, Michael Jain, Rawan G Faramand, Kayla Reid, Sae Bom Lee, Salvatore Corallo, Melanie Hidalgo-Vargas, Abhishek Kumar, Sanjay Chandrasekhar, Julio Chavez, Bijal Shah, Aleksandr Lazaryan, Farhad Khimani, Taiga Nishihori, Christina Bachmeier, Frederick Locke, Guilherme Oliveira, Mohammed Alomar, Marco L Davila
Journal: Circulation (2022)

Introduction: Chimeric Antigen receptor T- Cells (CAR-T) are novel therapy for various malignancies, including lymphoma. Cardiotoxicity such as heart failure, arrhythmia, and acute coronary syndrome frequently occurs in the setting of cytokine release syndrome (CRS). Hypothesis: We aimed to investigate the changes in inflammatory cytokines in patients who develop cardiotoxicity after CAR-T therapy. Methods: This was a prospective observational cohort study involving patients diagnosed with lymphoma treated with CAR-T therapy (axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel). Serum cytokines interleukin (IL)-2, IL-6, IL-15, IFN-gamma, TNF-alpha, GM-CSF, and angiopoietin 1 &amp; 2 were tested before lymphodepletion and daily during index hospitalization. Cytokines were analyzed using the ELLA Immunoassay system (SimplePlex, Protein Simple) and reported in pg/mL. Cardiac events were adjudicated by a cardio-oncology team. Results: Fifty-three patients with a complete set of cytokine levels were analyzed. There were 9 cardiac events after CAR-T (8 atrial fibrillation and 1 cardiomyopathy). Patients with cardiac events were older and had higher baseline creatinine level and left atrial volume. All cardiac events occurred in patients who had low-grade CRS (5 Grade 1 and 4 Grade 2 CRS). Tocilizumab was given to seven patients. Pre-CAR-T baseline inflammatory cytokine levels were not different in the cardiac event group. However, median peak IFN-gamma, IL-6, and IL-15 levels were higher median in the cardiac event group (Figure 1). Conclusions: In the setting of CAR-T, the elevation of multiple pro-inflammatory pathways from cytokine release syndrome may be related to the adverse cardiac events, including atrial fibrillation. Further studies are needed to identify and investigate the role of specific inflammatory mediators in cardiac events after CAR-T therapy.
Abstract 10198: Using Weakly Supervised Machine Learning to Label Atrial Fibrillation in Real-World Intensive Care Unit Telemetry Data
Authors: Sydney R Rooney, Roman Kaufman, Mononito Goswami, Michael R Pinsky, J. Kyle Miller, Salah Al-Zaiti, Artur Dubrawski, Gilles Clermont
Journal: Circulation (2022)

Introduction: Atrial fibrillation (AF) alerts from clinical monitoring systems are often inaccurate. Recently reported AF detectors utilize curated, publicly-available databases for model training. Real-world data rather than curated databases would be better suited to improve upon these inaccuracies, but labeling high-frequency waveform data over ICU stays would require significant clinician hours. Hypothesis: We hypothesize that AF can be accurately and efficiently labeled in stored, real-world telemetry data through clinician-made heuristics describing AF that inform a weakly supervised AF detection model. Methods: We examined high-frequency telemetry data from 72 beds in a tertiary care center using a commercial monitoring system. Previously described time- and frequency-domain heart rate variability features centered over 10-second segments were calculated. K-means clustering was applied over RR interval Poincaré plots (RR n vs RR n+1 ) to describe rhythmic patterns. Over 20 features and associated clinician-driven heuristics delineating AF from other rhythms informed a weakly supervised AF labeling algorithm. Performance was evaluated on ~100 independent, hand-labeled segments. Results: Over 10,000 10-second telemetry segments from 657 ICU patients were used to train our weakly supervised model. The model had an AUC of 0.91 and accuracy of 88%. Positive predictive value and sensitivity were 0.67 and 0.82 for AF segments and 0.95 and 0.89 for non-AF segments. Compared to our commercial monitoring system, our model demonstrated significant improvement in AF F1 score (0.73 vs 0.56) with the same F1 score for non-AF rhythms (0.92). The most influential features on AUC included a standard measure of heart rate variability (pNN20) and rhythm clustering pattern (sum of squared error). Conclusions: We demonstrated a time-saving means of labeling AF in a large, real-world telemetry database through weak supervision. Features describing heart rate variability and RR interval irregularity through clustering techniques led to intuitive, clinically sound rules for identifying AF. Our contribution permits the creation of much larger, more clinically relevant datasets with AF clearly labeled for improved study and care of this population.
Abstract 10337: Early Adaptation of the Mitral Valve After St-Elevation Myocardial Infarction
Authors: Isabelle Senechal Dumais, Valerie Deschenes, Ons Marsit, Sandra Hadjadj, Marie-Annick Clavel, Philippe Pibarot, Rebecca Bucknell, Andreanne Vallerand, Mark Handschumacher, Robert Levine, Jonathan Beaudoin
Journal: Circulation (2022)

Introduction: Ischemic mitral regurgitation (IMR) is associated with worse outcomes and higher mortality after myocardial infarction (MI). Clinical observations and experimental data have shown that mitral valve leaflets have the potential to enlarge over time to compensate left ventricular remodeling and prevent IMR. Previous animal studies have demonstrated that MI is associated with fibrotic changes in the mitral valve leaflets and prevent this adaptive compensation. However, the timing of mitral valve geometric changes are not well described. While previous data shows an increase in leaflet size at 6 and 12 months after MI, its short-term evolution after an ischemic event is not well documented. Methods: Twenty-two patients with ST-elevation myocardial infarction and initial left ventricular ejection fraction ≤ 45% were enrolled in Quebec Heart and Lung Institute. Participants had 3D transthoracic echocardiography (TTE) at baseline and 3 months, as well as cardiac magnetic resonance (CMR) at 3-month follow-up. Mitral valve leaflet size was measured from the 3D TTE using a custom software (Omni4D). CMR was used to derive left ventricular volumes, function and mitral regurgitant volume. Significant IMR was defined as a mitral regurgitant fraction ≥ 15% derived from the 3-month CMR. Results: Twenty-one of the 22 patients completed the imaging follow-up. Left ventricular ejection fraction at 3 months was 53 ± 10% (range from 37 to 69%). Eight patients (38%) had mild IMR at 3 months. Mitral valve surface area was significantly increased at 3 months compared with baseline for patients without IMR (10.96 ± 1.78 cm 2 vs 9.51 ± 1.62 cm 2 ; p = 0.001). Valve enlargement vs baseline was significantly greater in patients without IMR (+17 ± 13% vs -5 ± 4% for those with IMR at follow-up, p=0.0007). Conclusions: Mitral valvular surface increases within the first few months after MI, but not in all patients. Adequate valve enlargement seems related to the absence of IMR at 3 months.
Abstract 10537: A Comparison of Endothelial Nitric Oxide Synthase(eNOS)-Based Platelet Subpopulation Ratios and Platelet VEGF Content Within Covid-19
Authors: Amir Asgari, Paul Jurasz
Journal: Circulation (2022)

Background: Nitric oxide (NO) regulates both thrombosis and vascular leakage, two of the major complications of severe Covid19. Platelet-derived NO inhibits adhesion/aggregation and within microvascular endothelial cells NO-signalling mediates vascular endothelial growth factor (VEGF/VPF)-induced permeability. Recently, we identified novel platelet subpopulations with a differential ability to produce NO and the presence/absence of endothelial nitric oxide synthase (eNOS). We showed that eNOS-negative (eNOS neg ) platelets initiate adhesion and aggregation, while eNOS-positive (eNOS pos ) platelets limit aggregate growth. As inflammatory cytokines are known to counter-regulate eNOS and VEGF expression, we hypothesized that the ratio of eNOS-negative to -positive platelets may be increased in COVID-19 patients along with their VEGF content. Aims: To determine the eNOS-positive to -negative platelet ratio and platelet VEGF levels within the blood of hospitalized COVID-19 patients. Methods: Platelets were isolated from age- and sex-matched COVID-19 patients (ICU and non-ICU) and COVID-negative healthy controls. Isolated platelets were intracellularly stained for eNOS, VEGF, and for surface CD62P and analyzed using flow cytometry. A multiplex assay was used to measure plasma cytokines. Results: The percentage of eNOS neg platelets within the blood of COVID-19 patients (ICU and non-ICU) was higher than that within healthy controls and their levels correlated with disease severity (81.2±2.8% ICU vs. 66.0 ±3.1% non-ICU vs. 6.1± 1.3% controls, P -value &lt; 0.0001). Accordingly, the percentage of eNOS pos platelets in COVID-19 patients was lower compared to controls, while the platelet VEGF content and surface CD62P of COVID-19 patients in ICU was higher than that of healthy controls. Further, COVID-19 patients demonstrated higher TNFα, IL-6, and IL-1β plasma concentrations than controls. Conclusion: Preliminary data suggests that eNOS-negative to -positive platelet ratios and VEGF content increase with COVID-19 severity, potentially predisposing patients to thrombosis and enhanced vascular permeability upon platelet activation. These platelet changes may be due to the actions of inflammatory cytokines on megakaryocytes.
Abstract 10494: Proteomic Assessment of Novel Kidney Function Biomarkers in Heart Failure: A Community Study
Authors: Joe J Shearer, Ho Young Park, Jungnam Joo, Kayode O Kuku, Suzette J Bielinski, Sheila M Manemann, Veronique L Roger
Journal: Circulation (2022)

Introduction: Heart failure (HF) is a complex syndrome with high mortality often associated with impaired kidney function. Estimated glomerular filtration rate (eGFR) is central to kidney function assessment in HF. However, novel proteins related to kidney function (lipocalin 2 [LCN2], macrophage inhibitory cytokine 1 [MIC1], T cell immunoglobulin and mucin domain 1 [TIM1]) may improve risk stratification of HF patients, beyond eGFR. Their prognostic contribution remain to be fully explored. Hypothesis: Proteomic assessment of kidney function biomarkers improves risk stratification in HF. Methods: Clinical data and biospecimens were collected from a HF community cohort in Southeastern Minnesota from 2003-2012. Serum creatinine was measured in 1,388 patients and eGFR was calculated with the 2021 Chronic Kidney Disease (CKD) Epidemiology Collaboration equation. CKD was defined as an eGFR &lt;60 mL/min/1.73m 2 . Plasma proteins were measured using the SomaLogic aptamer-based technology SomaScan®. In HF patients with and without CKD, Cox proportional hazard models were used to estimate the association between kidney function biomarkers and mortality, after adjustment for Meta-Analysis Global Group in Chronic HF (MAGGIC) risk score. Results: At HF index, patients were on average 75±13 years of age and 48% female. Patients had a median eGFR of 57 mL/min/1.73m 2 and 64% had CKD. Adjusted geometric mean levels of LCN2, MIC1, and TIM1 levels were 20-30% higher in patients with CKD. Patients with CKD were at higher risk of dying (HR 1.6, 95% CI 1.4-1.8). Patients with above median levels of LCN2, TIM1, MIC1 were at higher risk of dying, irrespective of CKD (See Figure). Conclusions: In a HF community cohort, several novel kidney function biomarkers provided further risk stratification in patients with and without CKD.
Abstract 10285: Prognostic Value of Provocative Spasm Test in Patients With Myocardial Infarction With and Without Obstructive Coronary Arteries
Authors: Takaya Ozawa, Kenji Goto, Katsuya Miura, Tomonari Kimura, Kazunari Kobayashi, Yuetsu Kikuta, katsumasa sato, Masahiro Taniguchi, Shigeki Hiramatsu, HIDEO TAKEBAYASHI, Seiichi Haruta
Journal: Circulation (2022)

Introduction : Coronary spasm potentially contributes to the pathogenesis of acute myocardial infarction (MI) with obstructive coronary artery disease (MICAD) and particularly warrants close consideration in MI with non-obstructive coronary arteries (MINOCA). However, there are limited data concerning the impact of coronary spasm in acute myocardial infarction (AMI). We aimed to assess the prognostic impact of provocative coronary spasm in both MICAD and MINOCA. Methods: Of 1,101 AMI patients admitted to our hospital from January 2012 to December 2019, 267 AMI patients (MICAD: n=198, MINOCA: n=69) who underwent emergency CAG and invasive provocative spasm test were assessed. The primary endpoint was a composite of major adverse cardiac events (MACE), defined as cardiovascular death, acute coronary syndrome, or revascularization. The median follow-up duration was 48 months. Results: Provocative test was positive in 143 (72.2%) of MICAD group and 33 (47.8%) of MINOCA group. In MICAD group, spasm-positive patients had a significantly higher occurrence of both MACE [27 (18.9%) vs. 4 (7.3%); p=0.0413] and Revascularization [25 (17.5%) vs. 3 (5.5%); p=0.0296] compared to spasm-negative patients. In MINOCA group, MACE occurred only in patients with spasm-positive [4 (12.1%) vs. 0 (0%); p=0.0473]. Among the 4 groups based on the type of MI (MICAD or MINOCA) and the presence of provoked coronary spasm, there was a significant difference in the MACE-free survival rate, with the lowest rate observed for MICAD patients with spasm-positive (log rank P=0.0111). In a Multivariable analysis, provoked coronary spasm was significantly associated with MACE in MICAD group (hazard ratio, 3.37;95% CI, 1.20-12.10; P=0.0189). Conclusions: Provocative spasm test could provide prognostic stratification for AMI patients.